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High-mobility group box-1 as an autocrine trophic factor in white matter stroke

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dc.contributor.authorChoi, JY-
dc.contributor.authorCui, Y-
dc.contributor.authorChowdhury, ST-
dc.contributor.authorKim, BG-
dc.date.accessioned2018-08-24T01:49:08Z-
dc.date.available2018-08-24T01:49:08Z-
dc.date.issued2017-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/15949-
dc.description.abstractMaintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHBrain Ischemia/metabolism-
dc.subject.MESHCells, Cultured-
dc.subject.MESHDemyelinating Diseases/metabolism-
dc.subject.MESHEndothelin-1/metabolism-
dc.subject.MESHHMGB1 Protein/metabolism-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMyelin Sheath/metabolism-
dc.subject.MESHOligodendroglia/metabolism-
dc.subject.MESHSignal Transduction/physiology-
dc.subject.MESHStroke/metabolism-
dc.subject.MESHToll-Like Receptor 2/metabolism-
dc.subject.MESHWhite Matter/metabolism-
dc.titleHigh-mobility group box-1 as an autocrine trophic factor in white matter stroke-
dc.typeArticle-
dc.identifier.pmid28584116-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488940/-
dc.contributor.affiliatedAuthor최, 준영-
dc.contributor.affiliatedAuthor최, 월선-
dc.contributor.affiliatedAuthor김, 병곤-
dc.type.localJournal Papers-
dc.identifier.doi10.1073/pnas.1702035114-
dc.citation.titleProceedings of the National Academy of Sciences of the United States of America-
dc.citation.volume114-
dc.citation.number25-
dc.citation.date2017-
dc.citation.startPageE4987-
dc.citation.endPageE4995-
dc.identifier.bibliographicCitationProceedings of the National Academy of Sciences of the United States of America, 114(25). : E4987-E4995, 2017-
dc.identifier.eissn1091-6490-
dc.relation.journalidJ000278424-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
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